Kotake H, Igawa O, Miyamoto J, Hasegawa J, Kosaka T, Furuse T, Mashiba H
Arzneimittelforschung. 1987 Apr;37(4):424-7.
Effect of 1-[3-isobutoxy-2-(benzylphenyl) amino]propyl pyrrolidine hydrochloride (bepridil), a new antianginal agent, on membrane potentials and membrane currents of sinoatrial node cells of rabbits was examined using conventional microelectrode and double microelectrode voltage clamp methods. Bepridil at a concentration of 10 mumol/l caused an increase in spontaneous cycle length, and a decrease in maximum rate of rise of the action potential and action potential amplitude. The rate of diastolic depolarization (phase 4) was also decreased by the drug. In the voltage clamp experiment, bepridil reduced both the slow inward current (Isi) and the hyperpolarization activated current (Ih), and increased the recovery time constant of Isi, whereas the time-dependent potassium current (IK) was not altered significantly. The major effect, however, was the reduction of Isi. These electrophysiological findings suggest that bepridil has a depressant effect on the electrical activity of sinoatrial node mainly by mediating the depression of slow channel.
使用传统微电极和双微电极电压钳方法，研究了新型抗心绞痛药物1-[3-异丁氧基-2-(苄基苯基)氨基]丙基吡咯烷盐酸盐（苄普地尔）对兔窦房结细胞膜电位和膜电流的影响。浓度为10 μmol/l的苄普地尔可使自发周期长度增加，动作电位最大上升速率和动作电位幅度降低。该药还可降低舒张期去极化速率（第4相）。在电压钳实验中，苄普地尔可降低慢内向电流（Isi）和超极化激活电流（Ih），并增加Isi的恢复时间常数，而时间依赖性钾电流（IK）无明显改变。然而，主要作用是降低Isi。这些电生理结果表明，苄普地尔主要通过介导慢通道的抑制对窦房结电活动产生抑制作用。
